In a continuing effort to improve the subtype selectivity and agonist potency of estrogen receptor β (ERβ) ligands, we have designed and developed a thus far unexplored structural series obtained by molecular refinements of monoaryl-substituted salicylaldoximes (Salaldox B). The most interesting compounds in this series (2c, d) show remarkably high ERβ-binding affinities, with Ki values reaching the sub-nanomolar range (Ki=0.38 nM for 2c and 0.57 nM for 2d), and have very high levels of ERβ-subtype selectivity. Both compounds show a potent full agonist character on ERβ (EC50=0.23 nM for 2c and 1.3 nM for 2d). Furthermore, 2d shows a remarkable functional subtype selectivity, with a β/α transcription potency ratio 50-fold higher than that of estradiol.
|Autori:||S. BERTINI; A. DE CUPERTINIS; C. GRANCHI; B. BARGAGLI; T. TUCCINARDI; A. MARTINELLI; M. MACCHIA; J. R. GUNTHER; K. E. CARLSON; J. A. KATZENELLENBOGEN; F. MINUTOLO|
|Titolo:||Selective and potent agonists for estrogen receptor beta derived from molecular refinements of salicylaldoximes|
|Anno del prodotto:||2011|
|Digital Object Identifier (DOI):||10.1016/j.ejmech.2011.03.030|
|Appare nelle tipologie:||1.1 Articolo in rivista|